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RNAi mediated IL-6 in vitro knockdown in psoriasis skin model with topical siRNA delivery system based on liquid crystalline phase

[Display omitted] Gene therapy by RNA interference (RNAi) is a post-transcriptional silencing process that can suppress the expression of a particular gene and it is a promising therapeutic approach for the treatment of many severe diseases, including cutaneous disorders. However, difficulties relat...

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Published in:European journal of pharmaceutics and biopharmaceutics 2016-08, Vol.105, p.50-58
Main Authors: Depieri, Lívia Vieira, Borgheti-Cardoso, Lívia Neves, Campos, Patrícia Mazureki, Otaguiri, Katia Kaori, Vicentini, Fabiana Testa Moura de Carvalho, Lopes, Luciana Biagini, Fonseca, Maria José Vieira, Bentley, M. Vitória Lopes Badra
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container_title European journal of pharmaceutics and biopharmaceutics
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creator Depieri, Lívia Vieira
Borgheti-Cardoso, Lívia Neves
Campos, Patrícia Mazureki
Otaguiri, Katia Kaori
Vicentini, Fabiana Testa Moura de Carvalho
Lopes, Luciana Biagini
Fonseca, Maria José Vieira
Bentley, M. Vitória Lopes Badra
description [Display omitted] Gene therapy by RNA interference (RNAi) is a post-transcriptional silencing process that can suppress the expression of a particular gene and it is a promising therapeutic approach for the treatment of many severe diseases, including cutaneous disorders. However, difficulties related to administration and body distribution limit the clinical use of small interfering RNA (siRNA) molecules. In this study, we proposed to use nanocarriers to enable siRNA application in the topical treatment of skin disorders. A siRNA nanodispersion based on liquid crystalline phase and composed of monoolein (MO), oleic acid (OA) and polyethylenimine (PEI) was developed and its physicochemical properties, efficiency of complexation and carrier/siRNA stability were assessed. Subsequently, cell viability, cellular uptake, in vitro skin irritation test using reconstructed human epidermis (RHE) and in vitro IL-6 knockdown in psoriasis skin model were evaluated. The results showed that the liquid crystalline nanodispersion is a promising topical delivery system for administration of siRNA, being able to overcome the limitations of the route of administration, as well those resulting from the characteristics of siRNA molecules. The formulation was effective at complexing the siRNA, presented high rate of cell uptake (∼90%), increased the skin penetration of siRNA in vitro, and did not cause skin irritation compared with Triton-X (a moderate irritant), resulting in a 4-fold higher viability of reconstructed human epidermis and a 15.6-fold lower release of IL-1α. A single treatment with the liquid crystalline nanodispersion carrying IL-6 siRNA for 6h was able to reduce the extracellular IL-6 levels by 3.3-fold compared with control treatment in psoriasis skin model. Therefore, liquid crystalline nanodispersion is a suitable nanocarrier for siRNA with therapeutic potential to suppress skin disease-specific genes. This study also highlights the applicability of reconstructed skin models in pharmaceutical field to evaluate the performance of delivery systems without the use of animal models.
doi_str_mv 10.1016/j.ejpb.2016.05.012
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identifier ISSN: 0939-6411
ispartof European journal of pharmaceutics and biopharmaceutics, 2016-08, Vol.105, p.50-58
issn 0939-6411
1873-3441
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subjects Gene Knockdown Techniques
Humans
In vitro knockdown
In Vitro Techniques
Interleukin-6 - genetics
Liquid crystalline nanodispersion
Models, Biological
Psoriasis - genetics
Reconstructed human epidermis
RNA Interference
RNA, Small Interfering - administration & dosage
Skin penetration
Small interfering RNA
Topical delivery system
title RNAi mediated IL-6 in vitro knockdown in psoriasis skin model with topical siRNA delivery system based on liquid crystalline phase
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